Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. We sequenced and analyzed the whole genomes of 27 HCCs, 25 of which were associated with hepatitis B or C virus infections, including two sets of multicentric tumors. Although no common somatic mutations were identified in the multicentric tumor pairs, their whole-genome substitution patterns were similar, suggesting that these tumors developed from independent mutations, although their shared etiological backgrounds may have strongly influenced their somatic mutation patterns. Statistical and functional analyses yielded a list of recurrently mutated genes. Multiple chromatin regulators, including ARID1A, ARID1B, ARID2, MLL and MLL3, were mutated in ～50% of the tumors. Hepatitis B virus genome integration in the TERT locus was frequently observed in a high clonal proportion. Our whole-genome sequencing analysis of HCCs identified the influence of etiological background on somatic mutation patterns and subsequent carcinogenesis, as well as recurrent mutations in chromatin regulators in HCCs.     

Using human pluripotent stem cells to untangle neurodegenerative disease mechanisms

Human pluripotent stem cells, including embryonic (hES) and induced pluripotent stem cells (hiPS), retain the ability to self-renew indefinitely, while maintaining the capacity to differentiate into all cell types of the nervous system. While human pluripotent cell-based therapies are unlikely to arise soon, these cells can currently be used as an inexhaustible source of committed neurons to perform high-throughput screening and safety testing of new candidate drugs. Here, we describe critically the available methods and molecular factors that are used to direct the differentiation of hES or hiPS into specific neurons. In addition, we discuss how the availability of patient-specific hiPS offers a unique opportunity to model inheritable neurodegenerative diseases and untangle their pathological mechanisms, or to validate drugs that would prevent the onset or the progression of these neurological disorders.     

Practical Contributions of the Systems-Based Evolutionary Learning Laboratory to Knowledge and Stakeholder Management

This paper reports on a case study on improving the quality of life for women smallholder farmers in Vietnam, using the systems-based Evolutionary Learning Laboratory (ELLab) approach. The study aims to provide evidence of practical contributions of the ELLab to project stakeholder and knowledge management through the case study. A transformative learning framework was developed to provide initial reflections on the planning phase of the project. Practical contributions of the ELLab process to stakeholder identification and management, and knowledge creation during project planning and implementation are discussed. Strong evidence was found of transformations in awareness and perspectives amongst project actors that subsequently led to systemic and executable action plans. This clearly proved the value of the ELLab approach in informal transformative learning.     

Rapid removal of Chernobyl fallout from Mediterranean surface waters by biological activity

The sinking of particulate organic matter from the euphotic zone is an important pathway for the vertical transport of many elements and organic compounds in the sea. Many natural and artificial radionuclides in surface waters are readily adsorbed onto suspended particles and are presumably scavenged and removed to depth on time scales commensurate with both particle sinking rate and retention time of the radionuclide on the particle. Previously, abyssal benthic organisms from the northeast Pacific were found to contain short-lived fission products which entered the sea surface as fallout from nuclear testing. The presence of these radionuclides at great depth could not be explained by Stokesian settling of small fallout particles and it was hypothesized that zooplankton grazing in the surface layers packaged these particle-reactive radionuclides into large, relatively dense faecal pellets which rapidly sank to depth. We report here data from a time-series sediment trap experiment and concomitant zooplankton collections which show conclusively that Chernobyl radioactivity, in particular the rare earth nuclides 141Ce and 144Ce, entering the Mediterranean as a single pulse, was rapidly removed from surface waters and transported to 200 m in a few days primarily by zooplankton grazing.     

Complex organic matter in Titan's atmospheric aerosols from in situ pyrolysis and analysis

Aerosols in Titan's atmosphere play an important role in determining its thermal structure. They also serve as sinks for organic vapours and can act as condensation nuclei for the formation of clouds, where the condensation efficiency will depend on the chemical composition of the aerosols. So far, however, no direct information has been available on the chemical composition of these particles. Here we report an in situ chemical analysis of Titan's aerosols by pyrolysis at 600 degrees C. Ammonia (NH3) and hydrogen cyanide (HCN) have been identified as the main pyrolysis products. This clearly shows that the aerosol particles include a solid organic refractory core. NH3 and HCN are gaseous chemical fingerprints of the complex organics that constitute this core, and their presence demonstrates that carbon and nitrogen are in the aerosols.